nm23—Relationship to the metastatic potential of breast carcinoma cell lines, primary human xenografts, and lymph node negative breast carcinoma patients

BACKGROUND Since the discovery of nm23 (nonmetastatic) by Steeg et al. in 1988, a number of tumor cohort studies have shown an inverse relationship between the levels of expression of the nm23‐H1 protein and disease aggressiveness and tumor metastatic potential. METHODS The relationship between the...

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Veröffentlicht in:Cancer 1997-03, Vol.79 (6), p.1158-1165
Hauptverfasser: Russell, Rosalind Lee, Geisinger, Kim R., Mehta, Rajeshwari R., White, Wain L., Shelton, Brent, Kute, Timothy Edward
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container_end_page 1165
container_issue 6
container_start_page 1158
container_title Cancer
container_volume 79
creator Russell, Rosalind Lee
Geisinger, Kim R.
Mehta, Rajeshwari R.
White, Wain L.
Shelton, Brent
Kute, Timothy Edward
description BACKGROUND Since the discovery of nm23 (nonmetastatic) by Steeg et al. in 1988, a number of tumor cohort studies have shown an inverse relationship between the levels of expression of the nm23‐H1 protein and disease aggressiveness and tumor metastatic potential. METHODS The relationship between the expression of nm23 protein and the metastatic potential of human breast carcinoma was analyzed in cell lines, xenografts, and in a retrospective lymph node negative breast carcinoma population. The lymph node negative breast carcinoma study was comprised of 40 patients: 19 with nonrecurrent and 21 with recurrent disease. The 40 patients were matched according to age, cathepsin D, tumor size, percent S‐phase, DNA ploidy, steroid receptor status, and tumor grade. Nm23‐H1 protein levels in cell lines and xenografts were analyzed quantitatively using Western blot analyses and semiquantitatively in tissue sections using immunocytochemistry. Immunocytochemical analysis of lymph node negative breast tumors was graded as the percent of tumor staining positive for nm23 and the intensity of staining. The metastatic potentials of the cell lines and xenografts were assessed as the ability to form metastatic lesions in nude mice. In the lymph node negative breast carcinoma patients, the metastatic potential was characterized as the incidence of breast carcinoma recurrence. RESULTS The MCF‐7 cell line expressed four‐ and tenfold higher levels of nm23‐H1 than the highly metastatic MDA‐MB‐435 and MDA‐MB‐231 cells, respectively. Among the xenografts and cell lines, there was an inverse correlation between nm23‐H1 expression and metastatic potential in athymic nude mice (correlation coefficient [R] = ‐0.51). The differences between the levels of nm23‐H1 among the metastatic and nonmetastatic cell lines and xenografts were not statistically significant. Statistical analyses indicated that neither the intensity nor the percent of tumor staining positive for nm23 expression was correlated to the recurrence of breast carcinoma in the lymph node negative patient population that had been matched for other clinical prognostic markers. CONCLUSIONS There was an inverse correlation (R = ‐0.51) between the levels of nm23‐H1 expression in cell lines and xenografts and the metastatic potential in nude mice. In the retrospective lymph node negative breast carcinoma population, no clear association was demonstrated between the expression of nm23 and breast carcinoma recurrence. This observation
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METHODS The relationship between the expression of nm23 protein and the metastatic potential of human breast carcinoma was analyzed in cell lines, xenografts, and in a retrospective lymph node negative breast carcinoma population. The lymph node negative breast carcinoma study was comprised of 40 patients: 19 with nonrecurrent and 21 with recurrent disease. The 40 patients were matched according to age, cathepsin D, tumor size, percent S‐phase, DNA ploidy, steroid receptor status, and tumor grade. Nm23‐H1 protein levels in cell lines and xenografts were analyzed quantitatively using Western blot analyses and semiquantitatively in tissue sections using immunocytochemistry. Immunocytochemical analysis of lymph node negative breast tumors was graded as the percent of tumor staining positive for nm23 and the intensity of staining. The metastatic potentials of the cell lines and xenografts were assessed as the ability to form metastatic lesions in nude mice. In the lymph node negative breast carcinoma patients, the metastatic potential was characterized as the incidence of breast carcinoma recurrence. RESULTS The MCF‐7 cell line expressed four‐ and tenfold higher levels of nm23‐H1 than the highly metastatic MDA‐MB‐435 and MDA‐MB‐231 cells, respectively. Among the xenografts and cell lines, there was an inverse correlation between nm23‐H1 expression and metastatic potential in athymic nude mice (correlation coefficient [R] = ‐0.51). The differences between the levels of nm23‐H1 among the metastatic and nonmetastatic cell lines and xenografts were not statistically significant. Statistical analyses indicated that neither the intensity nor the percent of tumor staining positive for nm23 expression was correlated to the recurrence of breast carcinoma in the lymph node negative patient population that had been matched for other clinical prognostic markers. CONCLUSIONS There was an inverse correlation (R = ‐0.51) between the levels of nm23‐H1 expression in cell lines and xenografts and the metastatic potential in nude mice. In the retrospective lymph node negative breast carcinoma population, no clear association was demonstrated between the expression of nm23 and breast carcinoma recurrence. This observation suggests the nm23 expression does not predict outcome in lymph node negative breast carcinoma patients. Cancer 1997; 79:1158‐65. © 1997 American Cancer Society. Analyses of the levels of nm23 protein were performed on breast tumor cell lines, xenografts, and a retrospective lymph node negative breast carcinoma population using immunohistochemical and/or Western blot methods. No significant correlation was observed between the levels of nm23 and the metastatic potential of these breast tumor populations.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/(SICI)1097-0142(19970315)79:6&lt;1158::AID-CNCR14&gt;3.0.CO;2-Z</identifier><identifier>PMID: 9070493</identifier><identifier>CODEN: CANCAR</identifier><language>eng</language><publisher>New York: John Wiley &amp; Sons, Inc</publisher><subject>Aged ; Animals ; Biological and medical sciences ; Blotting, Western ; Breast ; Breast carcinoma ; Breast Neoplasms - chemistry ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; clinical ; Female ; Gene Expression Regulation, Neoplastic ; Gynecology. Andrology. Obstetrics ; Humans ; immunohistochemistry ; lymph node‐negative ; Lymphatic Metastasis ; Mammary gland diseases ; Medical sciences ; metastasis ; Mice ; Mice, Nude ; Middle Aged ; Monomeric GTP-Binding Proteins ; Neoplasm Metastasis ; Neoplasm Recurrence, Local - chemistry ; Neoplasm Recurrence, Local - genetics ; nm23 ; NM23 Nucleoside Diphosphate Kinases ; Nucleoside-Diphosphate Kinase ; Prognosis ; Transcription Factors - analysis ; Transcription Factors - genetics ; Transplantation, Heterologous ; Tumor Cells, Cultured - pathology ; Tumors</subject><ispartof>Cancer, 1997-03, Vol.79 (6), p.1158-1165</ispartof><rights>Copyright © 1997 American Cancer Society</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3334-80fc2c55e2d710f177e42e3b195219e5ef77116a9dbfab8d3f9a33d06f18af863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2F%28SICI%291097-0142%2819970315%2979%3A6%3C1158%3A%3AAID-CNCR14%3E3.0.CO%3B2-Z$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2F%28SICI%291097-0142%2819970315%2979%3A6%3C1158%3A%3AAID-CNCR14%3E3.0.CO%3B2-Z$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=2639263$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9070493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Russell, Rosalind Lee</creatorcontrib><creatorcontrib>Geisinger, Kim R.</creatorcontrib><creatorcontrib>Mehta, Rajeshwari R.</creatorcontrib><creatorcontrib>White, Wain L.</creatorcontrib><creatorcontrib>Shelton, Brent</creatorcontrib><creatorcontrib>Kute, Timothy Edward</creatorcontrib><title>nm23—Relationship to the metastatic potential of breast carcinoma cell lines, primary human xenografts, and lymph node negative breast carcinoma patients</title><title>Cancer</title><addtitle>Cancer</addtitle><description>BACKGROUND Since the discovery of nm23 (nonmetastatic) by Steeg et al. in 1988, a number of tumor cohort studies have shown an inverse relationship between the levels of expression of the nm23‐H1 protein and disease aggressiveness and tumor metastatic potential. METHODS The relationship between the expression of nm23 protein and the metastatic potential of human breast carcinoma was analyzed in cell lines, xenografts, and in a retrospective lymph node negative breast carcinoma population. The lymph node negative breast carcinoma study was comprised of 40 patients: 19 with nonrecurrent and 21 with recurrent disease. The 40 patients were matched according to age, cathepsin D, tumor size, percent S‐phase, DNA ploidy, steroid receptor status, and tumor grade. Nm23‐H1 protein levels in cell lines and xenografts were analyzed quantitatively using Western blot analyses and semiquantitatively in tissue sections using immunocytochemistry. Immunocytochemical analysis of lymph node negative breast tumors was graded as the percent of tumor staining positive for nm23 and the intensity of staining. The metastatic potentials of the cell lines and xenografts were assessed as the ability to form metastatic lesions in nude mice. In the lymph node negative breast carcinoma patients, the metastatic potential was characterized as the incidence of breast carcinoma recurrence. RESULTS The MCF‐7 cell line expressed four‐ and tenfold higher levels of nm23‐H1 than the highly metastatic MDA‐MB‐435 and MDA‐MB‐231 cells, respectively. Among the xenografts and cell lines, there was an inverse correlation between nm23‐H1 expression and metastatic potential in athymic nude mice (correlation coefficient [R] = ‐0.51). The differences between the levels of nm23‐H1 among the metastatic and nonmetastatic cell lines and xenografts were not statistically significant. Statistical analyses indicated that neither the intensity nor the percent of tumor staining positive for nm23 expression was correlated to the recurrence of breast carcinoma in the lymph node negative patient population that had been matched for other clinical prognostic markers. CONCLUSIONS There was an inverse correlation (R = ‐0.51) between the levels of nm23‐H1 expression in cell lines and xenografts and the metastatic potential in nude mice. In the retrospective lymph node negative breast carcinoma population, no clear association was demonstrated between the expression of nm23 and breast carcinoma recurrence. This observation suggests the nm23 expression does not predict outcome in lymph node negative breast carcinoma patients. Cancer 1997; 79:1158‐65. © 1997 American Cancer Society. Analyses of the levels of nm23 protein were performed on breast tumor cell lines, xenografts, and a retrospective lymph node negative breast carcinoma population using immunohistochemical and/or Western blot methods. No significant correlation was observed between the levels of nm23 and the metastatic potential of these breast tumor populations.</description><subject>Aged</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Breast</subject><subject>Breast carcinoma</subject><subject>Breast Neoplasms - chemistry</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>clinical</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>immunohistochemistry</subject><subject>lymph node‐negative</subject><subject>Lymphatic Metastasis</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Middle Aged</subject><subject>Monomeric GTP-Binding Proteins</subject><subject>Neoplasm Metastasis</subject><subject>Neoplasm Recurrence, Local - chemistry</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>nm23</subject><subject>NM23 Nucleoside Diphosphate Kinases</subject><subject>Nucleoside-Diphosphate Kinase</subject><subject>Prognosis</subject><subject>Transcription Factors - analysis</subject><subject>Transcription Factors - genetics</subject><subject>Transplantation, Heterologous</subject><subject>Tumor Cells, Cultured - pathology</subject><subject>Tumors</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd-K1DAYxYso6-zqIwi5ENkFO-ZP2zSjLAz138DiwKqg68VH2n7ZqbRpbTrq3PkQ3vl2PokpU-dmBS9CyPlOTk74BcGS0TmjlD85fbvKVmeMKhlSFvFTppSkgsVnUi2SZ4zF6WKxXD0PszfZJYvOxZzOs_VTHl7dCmaHW7eDGaU0DeNIfLgbHDv32R8lj8VRcKSopJESs-CXbbj4_ePnJdZ6qFrrNlVHhpYMGyQNDtoNXi5I1w5oh0rXpDUk79HrpNB9Udm20aTAuiZ1ZdE9Jl1fNbrfkc220ZZ8R9te99oMfqJtSepd022IbUskFq999Fe8Gdd53b_m7gV3jK4d3p_2k-D9yxfvstfhxfrVKltehIUQIgpTagpexDHyUjJqmJQYcRQ5UzFnCmM0UjKWaFXmRudpKYzSQpQ0MSzVJk3ESfBon9v17ZctugGayo1_0hbbrQOZKkojEXvjx72x6FvnejQw_RYYhREcwAgORgQwIoC_4EAqSGAEB-DBwR4cCKCQrYHDlc9-MJXY5g2Wh-SJlJ8_nObaFbo2vbZF5Q42ngjll7d92tu-VTXubvT7f71_tpsU8QfWb8Yc</recordid><startdate>19970315</startdate><enddate>19970315</enddate><creator>Russell, Rosalind Lee</creator><creator>Geisinger, Kim R.</creator><creator>Mehta, Rajeshwari R.</creator><creator>White, Wain L.</creator><creator>Shelton, Brent</creator><creator>Kute, Timothy Edward</creator><general>John Wiley &amp; Sons, Inc</general><general>Wiley-Liss</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19970315</creationdate><title>nm23—Relationship to the metastatic potential of breast carcinoma cell lines, primary human xenografts, and lymph node negative breast carcinoma patients</title><author>Russell, Rosalind Lee ; Geisinger, Kim R. ; Mehta, Rajeshwari R. ; White, Wain L. ; Shelton, Brent ; Kute, Timothy Edward</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3334-80fc2c55e2d710f177e42e3b195219e5ef77116a9dbfab8d3f9a33d06f18af863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Aged</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Breast</topic><topic>Breast carcinoma</topic><topic>Breast Neoplasms - chemistry</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>clinical</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>immunohistochemistry</topic><topic>lymph node‐negative</topic><topic>Lymphatic Metastasis</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Middle Aged</topic><topic>Monomeric GTP-Binding Proteins</topic><topic>Neoplasm Metastasis</topic><topic>Neoplasm Recurrence, Local - chemistry</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>nm23</topic><topic>NM23 Nucleoside Diphosphate Kinases</topic><topic>Nucleoside-Diphosphate Kinase</topic><topic>Prognosis</topic><topic>Transcription Factors - analysis</topic><topic>Transcription Factors - genetics</topic><topic>Transplantation, Heterologous</topic><topic>Tumor Cells, Cultured - pathology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Russell, Rosalind Lee</creatorcontrib><creatorcontrib>Geisinger, Kim R.</creatorcontrib><creatorcontrib>Mehta, Rajeshwari R.</creatorcontrib><creatorcontrib>White, Wain L.</creatorcontrib><creatorcontrib>Shelton, Brent</creatorcontrib><creatorcontrib>Kute, Timothy Edward</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Russell, Rosalind Lee</au><au>Geisinger, Kim R.</au><au>Mehta, Rajeshwari R.</au><au>White, Wain L.</au><au>Shelton, Brent</au><au>Kute, Timothy Edward</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>nm23—Relationship to the metastatic potential of breast carcinoma cell lines, primary human xenografts, and lymph node negative breast carcinoma patients</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>1997-03-15</date><risdate>1997</risdate><volume>79</volume><issue>6</issue><spage>1158</spage><epage>1165</epage><pages>1158-1165</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><coden>CANCAR</coden><abstract>BACKGROUND Since the discovery of nm23 (nonmetastatic) by Steeg et al. in 1988, a number of tumor cohort studies have shown an inverse relationship between the levels of expression of the nm23‐H1 protein and disease aggressiveness and tumor metastatic potential. METHODS The relationship between the expression of nm23 protein and the metastatic potential of human breast carcinoma was analyzed in cell lines, xenografts, and in a retrospective lymph node negative breast carcinoma population. The lymph node negative breast carcinoma study was comprised of 40 patients: 19 with nonrecurrent and 21 with recurrent disease. The 40 patients were matched according to age, cathepsin D, tumor size, percent S‐phase, DNA ploidy, steroid receptor status, and tumor grade. Nm23‐H1 protein levels in cell lines and xenografts were analyzed quantitatively using Western blot analyses and semiquantitatively in tissue sections using immunocytochemistry. Immunocytochemical analysis of lymph node negative breast tumors was graded as the percent of tumor staining positive for nm23 and the intensity of staining. The metastatic potentials of the cell lines and xenografts were assessed as the ability to form metastatic lesions in nude mice. In the lymph node negative breast carcinoma patients, the metastatic potential was characterized as the incidence of breast carcinoma recurrence. RESULTS The MCF‐7 cell line expressed four‐ and tenfold higher levels of nm23‐H1 than the highly metastatic MDA‐MB‐435 and MDA‐MB‐231 cells, respectively. Among the xenografts and cell lines, there was an inverse correlation between nm23‐H1 expression and metastatic potential in athymic nude mice (correlation coefficient [R] = ‐0.51). The differences between the levels of nm23‐H1 among the metastatic and nonmetastatic cell lines and xenografts were not statistically significant. Statistical analyses indicated that neither the intensity nor the percent of tumor staining positive for nm23 expression was correlated to the recurrence of breast carcinoma in the lymph node negative patient population that had been matched for other clinical prognostic markers. CONCLUSIONS There was an inverse correlation (R = ‐0.51) between the levels of nm23‐H1 expression in cell lines and xenografts and the metastatic potential in nude mice. In the retrospective lymph node negative breast carcinoma population, no clear association was demonstrated between the expression of nm23 and breast carcinoma recurrence. This observation suggests the nm23 expression does not predict outcome in lymph node negative breast carcinoma patients. Cancer 1997; 79:1158‐65. © 1997 American Cancer Society. Analyses of the levels of nm23 protein were performed on breast tumor cell lines, xenografts, and a retrospective lymph node negative breast carcinoma population using immunohistochemical and/or Western blot methods. No significant correlation was observed between the levels of nm23 and the metastatic potential of these breast tumor populations.</abstract><cop>New York</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>9070493</pmid><doi>10.1002/(SICI)1097-0142(19970315)79:6&lt;1158::AID-CNCR14&gt;3.0.CO;2-Z</doi><tpages>8</tpages></addata></record>
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source MEDLINE; Wiley Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Online Library (Open Access Collection); Alma/SFX Local Collection
subjects Aged
Animals
Biological and medical sciences
Blotting, Western
Breast
Breast carcinoma
Breast Neoplasms - chemistry
Breast Neoplasms - genetics
Breast Neoplasms - pathology
clinical
Female
Gene Expression Regulation, Neoplastic
Gynecology. Andrology. Obstetrics
Humans
immunohistochemistry
lymph node‐negative
Lymphatic Metastasis
Mammary gland diseases
Medical sciences
metastasis
Mice
Mice, Nude
Middle Aged
Monomeric GTP-Binding Proteins
Neoplasm Metastasis
Neoplasm Recurrence, Local - chemistry
Neoplasm Recurrence, Local - genetics
nm23
NM23 Nucleoside Diphosphate Kinases
Nucleoside-Diphosphate Kinase
Prognosis
Transcription Factors - analysis
Transcription Factors - genetics
Transplantation, Heterologous
Tumor Cells, Cultured - pathology
Tumors
title nm23—Relationship to the metastatic potential of breast carcinoma cell lines, primary human xenografts, and lymph node negative breast carcinoma patients
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